Exhaled Carbon Dioxide in Healthy Term Infants Immediately after Birth Georg M. Schm€olzer, MD, PhD1,2,3,4,5, Stuart B. Hooper, PhD3, Connie Wong, RN2, C. Omar F. Kamlin, DSciMed2,5,6, and Peter G. Davis, MD2,5,6 Objective To measure exhaled carbon dioxide (ECO2) in term infants immediately after birth. Study design Infants >37 weeks gestation born at The Royal Women’s Hospital, Melbourne, Australia were eligible. A combined flow sensor and mainstream carbon dioxide (CO2) analyzer was placed in series proximal to a facemask to measure ECO2 and tidal volumes in the first 120 seconds after birth. Results Term infants (n = 20) with a mean (SD) birth weight of 2976 (697) g and gestational age of 38 (2) weeks were included. Infants took a median (range) 3 (1-8) breaths before ECO2 was detected. The median (range) of maximum ECO2 was 51 (40-73) mm Hg at 70 (21-106) seconds after birth. Within the first 10 breaths, CO2 increased from 0-27 (22-34) mm Hg. The median (IQR) tidal volume during the breaths without CO2 was 1.2 (0.8-3.1) mL/kg compared with 7.3 (3.2-10.9) mL/kg during the first 10 breaths where CO2 was exhaled. Conclusions The first breaths for an infant after birth did not contain ECO2. With aeration of the distal gas exchange regions, tidal volume and ECO2 significantly increased. ECO2 can be used to monitor lung aeration immediately after birth. (J Pediatr 2015;166:844-9).
B
efore birth, the airways are liquid-filled, and the lungs take no part in gas exchange, which occurs across the placenta.1,2 At birth, lung liquid has to be cleared from the airways to allow air entry and establishment of a functional residual capacity (FRC).1,2 Although much airway liquid can be removed before birth, a significant amount remains in the airways and its removal after birth is dependent on the infant’s respiratory effort.2 In the minutes after birth, the liquid within the airways is gradually cleared and replaced by air. Term and preterm infants use several different breathing patterns immediately after birth to achieve lung aeration.3 However, when infants fail to breathe adequately immediately after birth, it is important to apply positive pressure ventilation sufficient to facilitate gas exchange but without causing lung injury.4 At present, very little information is available to the clinician to assess the effectiveness of positive pressure ventilation.5,6 Clinicians lack feedback from either the patient or standard monitoring equipment to achieve the desired balance of aerating the distal gas exchange units (alveoli) without over-distending the lung thereby causing lung injury.7,8 Carbon dioxide (CO2) is produced in the tissues, transported to the lung, and exhaled from the lung. Therefore, CO2 can only be detected in expired gas if the lung is aerated, effective gas exchange has occurred, and adequate cardiac output is present.8-10 Hooper et al recently described how exhaled CO2 (ECO2) levels are an important indicator of ventilation of the distal gas exchange units.8 Several studies reported the use of ECO2 monitoring during neonatal transition to: (1) determine correct tube placement11,12; (2) identify airway obstruction13,14; (3) using CO2 targeting during mask ventilation15; or (4) assessing lung aeration in preterm infants.8-10,16 No study has reported ECO2 values in the first minutes after birth in term infants. The aim of the study was to measure the amount of ECO2 in term infants in the first 120 seconds after birth.
Methods All infants were born at The Royal Women’s Hospital, Melbourne, Australia, a tertiary perinatal center where 7300 infants are born each year. Infants who were >37 weeks postmenstrual age were eligible for the study. Consent was requested before birth and if the mother was not in established labor. Infants were excluded from final analysis if they had a congenital abnormality that might adversely affect their breathing. The Royal Women’s Hospital Research and Ethics Committees approved the study. The NICO Cardiopulmonary management system (Novametrix Medical System, Wallingford, Connecticut) consists of a combined CO2/flow sensor, which CO2 ECO2 FRC
Carbon dioxide Exhaled CO2 Functional residual capacity
From the 1Center for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Canada; 2Neonatal Services, The Royal Women’s Hospital; 3The Ritchie Center, Monash University, Melbourne, Australia; 4Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 5Critical Care Stream, Murdoch Children Research Institute; and 6Department of Obstetrics and Gynecology, The University of Melbourne, Melbourne, Australia Supported by the Laerdal Foundation for Acute Medicine (Stavanger, Norway). G.S. is supported in part by a Banting Postdoctoral Fellowship, Canadian Institute of Health Research. P.D. and S.H. are supported by an Australian National Health and Medical Research Council Practitioner and Principal Research Fellowship, respectively, and the Australian National Health and Medical Research Council Program (No. 384100). C.K. is supported by an Australian National Health and Medical Research Early Career Fellowship. S.H. was supported by the Victorian Government’s Operational Infrastructure Support Program. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.12.007
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Vol. 166, No. 4 April 2015 measured ECO2 by infrared absorbance and gas flow, tidal volume, respiratory rate, and airway pressures with a flow sensor. The dead space of the CO2/flow sensor is 1 mL. The CO2/flow sensor was attached to a facemask (Laerdal round mask; Laerdal, Stavanger, Norway). Immediately after birth, the infants were placed on the mother’s chest, and the facemask was placed on the infants face to cover the mouth and the nose. This procedure was performed before the cord was clamped. To minimize interference with parentinfant bonding and to allow standard assessments and monitoring of term infants at birth, we only took measurements for the first 120 seconds from birth. If there were any signs of respiratory compromise, the study was abandoned and respiratory support was given according to the Neonatal Resuscitation guidelines.4 Data Collection and Analyses All recordings in the delivery room were performed by G.S. Time of birth was defined as delivery of the whole baby. The signals of airway flow, tidal volume, airway pressure, and ECO2 were recorded at 200 Hz using Spectra physiological recording program (a customized neonatal respiratory physiology program). Demographic characteristics of study infants were recorded. A breath-by-breath analysis was performed manually for the duration of each recording. Tidal volume, inflation time, gas flow, and ECO2 were measured. Breaths were excluded if mask leak was >30%. The data are presented as mean ( SD) for normally distributed continuous variables and median (IQR) when the distribution was skewed. For all respiratory variables, the mean value for each infant was calculated first and then either the mean or median of the median calculated. The clinical characteristics and outcome variables were compared using
Student t-test for parametric and Mann-Whitney U-test for nonparametric comparisons for continuous variables, and c2 for categorical variables. ECO2 values during different breathing patterns were compared using repeated measures ANOVA with Bonferroni post-test. P values are 2-sided, and P < .05 was considered statistically significant. Statistical analyses were performed with Stata (Intercooled 10; StataCorp, College Station, Texas). The study was reported according to The Strengthening the Reporting of Observational Studies in Epidemiology statement guidelines.17
Results We included a convenience sample of 20 term infants. All infants initiated spontaneous breathing, and none required respiratory support, intubation, chest compressions, or epinephrine. The mean (SD) birth weight was 2976 (697) g, and gestational age 38 (2) weeks. Seven infants (35%) were male and the median (IQR) 1 and 5 minute Apgar scores were 9 (7; 9) and 9 (9; 10), respectively. A total of 1129 breaths were analyzed, with a median (IQR) of 54 (42-69) per infant. The face mask was placed over the baby’s mouth and nose at a median (IQR) of 5 (3-8) seconds after birth. CO2 ECO2 was first detected at a median (range) of 3 (1-8) breaths or 15 (12-22) seconds after birth (Table). Within the next 10 breaths, CO2 increased significantly to 27 (22-34) mm Hg in all infants (P < .0001) (Table and Figures 1 and 2). Three infants had significantly less measured ECO2 in the first 10 breaths compared with the other 17 infants (Table). Increases in ECO2 were associated with increases in tidal
Table. Tidal volume, exhaled CO2, and mask leak during the first 120 seconds ID number (n = 20) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Number of breaths without ECO2
VTe (mL/kg) without ECO2
VTe (mL/kg) from the first 10 breaths with ECO2
P values for comparison of VTe with and without CO2
3 3 8 4 1 1 8 2 1 0 2 5 1 5 1 1 2 1 0 2
0.9 (0.6-4.0) 0.9 (0.6-4.0) 2.5 (1.5-3.5) 0.8 (0.5-1.3) 3.7 0.8 2.1 (0.8-2.9) 0.5 0.3 0.7 (0.6-0.8) 0.9 (0.7-2.9) 0.6 1.6 (1.2-2.1) 3.1 6.3 0.6 0.3 0.8 (0.7-0.9)
11.4 (6.7-12.7) 12.1 (6.9-13.2) 13.4 (6.6-20.3) 7.7 (3.1-10.4) 10.7 (9.7-11.6) 1.1 (0.8-1.7) 6.3 (1.9-11.7) 9.6 (4.0-11.2) 2.5 (2.4-3.3) 4.6 (3.8-4.9) 7.0 (6.7-8.3) 12.5 (6.0-14.2) 3.7 (1.2-7.1) 1.4 (1.1-2.8) 10.8 (4.4-16.5) 1.9 (0.9-2.4) 11.0 (4.6-12.8) 2.4 (2.2-3.1) 4.6 (3.8-5.0) 7.8 (7.4-9.2)
.0078 .0084 .0015 .0289 .0165
.0076 .0032 .6163
.0076
ECO2 (mm Hg)
Mask leak (%)
21 (18-24)* 22.5 (13-25)* 31 (28-35)* 25 (20-26)* 29 (26-33)* 12 (8-14)* 50 (20-53)* 53 (50-57)* 34 (27-43)* 22 (18-30)* 27 (17-38)* 36 (35-40)* 29 (20-42)* 8 (7-10)* 26 (10-35)* 8.5 (7-10)* 52 (49-57)* 33 (27-42)* 22 (18-29)* 26 (17-37)*
23 (16) 22 (15) 33 (23) 24 (24) 20 (14) 38 (25) 43 (25) 26 (20) 12 (9) 36 (21) 27 (20) 17 (13) 24 (17) 27 (17) 34 (29) 28 (22) 26 (21) 12 (9) 35 (21) 26 (19)
ID, identification; VTe, expiratory tidal volume. Values are presented as median (IQR) unless indicated *mean (range).
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Vol. 166, No. 4 maximum ECO2 was 51 (40-73) mm Hg at 70 (21-106) seconds after birth. ECO2 at 60 and 120 seconds after birth was 41 (7) and 43 (10) mm Hg, respectively (Figure 1). Overall no difference in ECO2 between different breathing patterns was found. The median (IQR) ECO2 during expiratory breath hold was 38 (31-43) mm Hg vs 40 (30-47) mm Hg during slow expiration (Figure 3; available at www.jpeds. com), 33 (10-40) mm Hg during crying (Figure 4; available at www.jpeds.com), 35 (30-40) mm Hg during grunting, 35 (28-40) mm Hg during normal breaths (Figure 5), and 32 (26-40) mm Hg during panting, respectively.
Figure 1. Course of mean (SD) ECO2 (mm Hg) and VTe (mL/kg). Breaths after birth (0-1 = No CO2; 1-10 = the first 10 breaths with CO2; and at 60 and 120 seconds of recording). VTe, tidal volume.
volume in most (17/20) infants. Two infants did not show an increase in tidal volume before and after ECO2 was detected. Only 1 infant showed a decrease in expired tidal volume when ECO2 was first detected. The median (range) of
Tidal Volume Infants initiated spontaneous breathing at a median (range) of 9 (2-33) seconds after birth. The median (IQR) tidal volume during breaths without CO2 was 1.2 (0.8-3.1) mL/kg compared with 7.3 (3.2-10.9) mL/kg during the first 10 breaths where CO2 was exhaled (Table). The tidal volume at 60 and 120 seconds after birth was 5.4 (4) and 6.3 (3) mL/kg, respectively (Figure 1). Inspiration Time The median (IQR) inspiration time during breaths with no CO2 was similar compared with breaths with ECO2 0.19 (0.14-0.6) second vs 0.29 (0.24-0.34) second, respectively (P = .16). Gas Flow The inspired and expired gas flow significantly increased in the first 10 breaths with ECO2 compared with breaths with
Figure 2. Spontaneously breathing 38 weeks term infant with VTe breaths of 6.1-7.7 mL/kg. The ECO2 is around 5-10 mm Hg. Once the cord is clamped, spontaneous VTe are similar. However, a rapid increase in CO2 to 50-70 mm Hg is observed. 846
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Figure 5. Inspiration is identified by a steep incline in the gas flow wave and the VTe wave. The CO2 wave remains at baseline until the start of expiration, which can be identified with a sharp increase in the CO2 wave, a negative gas flow wave, and decline in VTe wave.
no CO2. Median (IQR) inspired flow when CO2 was not detected in the subsequent expired gas, was 30 (21-36) mL/s compared with 107 (49-147) mL/s when CO2 was detected (P = .003). Expiratory flow significantly increased from 42 ( 51 to 33) mL/s in breaths without CO2 compared with 92 ( 99 to 67) mL/s in breaths with CO2 (P = .023).
Discussion In utero, the airways are liquid-filled and the lungs do not take part in gas exchange, which occurs across the placenta. At birth, lung liquid has to be cleared from the airways to allow air entry to generate FRC and facilitate gas exchange. The majority of newborn infants cry at birth,18 leading to establishment of FRC and initiation of spontaneous breathing. Boon et al reported that only 5/20 asphyxiated newborn infants generated FRC with the first inflation,19 which is contrary to Vyas et al who reported that all 9 asphyxiated newborn infants established FRC with the first inflation.20 Studies of spontaneously breathing infants immediately after birth reported that the first breaths tend to be deeper and longer than subsequent breaths and are characterized by a short deep inspiration followed by a prolonged expiratory
phase. Vyas et al demonstrated that 15/16 infants were able to establish FRC with the first breath.20 However, it remains unclear whether those first breaths facilitate gas exchange. We have measured ECO2 immediately after birth (Figure 1) and before the umbilical cord was clamped (Figure 2) in 20 term infants to determine when lung aeration and gas exchange occurs. Compared with previously published studies, in our study, tidal volumes for the first breaths (Table) were small, ranging from 0.4-6.3 mL/kg. However, all infants took these first breaths while still attached to the umbilical cord (Figure 2). This may have indirectly contributed to the lower tidal volumes as a result of sustained placental gas exchange reducing the respiratory drive associated with increased circulating CO2 levels. Once the cord was clamped and tidal volume significantly increased, we were able to detect and measure ECO2 (Table). The volume of all consecutive breaths were similar to previously published studies.3,20-23 In addition, we observed a significant increase in expiratory and inspiratory gas flow in the first breaths with ECO2 compared with breaths without ECO2. Similar observation has been reported in phase contrast imaging studies.1,8 With each inspiratory effort, the air/liquid interface progressed deeper into the distal airways, thereby
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drawing air deeper into the respiratory tree.1 This could explain the significant increase in gas flow between unaerated and aerated breaths. In addition, end-expiratory lung volume increases with each breath, which could be an explanation for the observed larger tidal volumes in the breaths with ECO2. In the current study, all infants cried soon after birth, and we were able to record the first breath in all included infants. Overall, it took a median of 3 breaths until the first ECO2 was detected (Table). Once ECO2 was detected, levels increased significantly within the first 10 breaths (Figure 1). Similar results have been reported in studies measuring CO2 elimination in term and preterm infants.9,10,24-26 Our increase in ECO2 was related to increase in tidal volume, and inspiratory and expiratory gas flow. Overall, it took a median time of 70 seconds from birth until maximum ECO2 values were measured. These results are similar to previously reported values of CO2 elimination in term infants, which reached a maximum around 90-120 seconds after birth.25 However, preterm infants require a long period to achieve similar CO2 elimination values.10,24 We only recorded the first 120 seconds after birth, hence, we do not know if potentially higher ECO2 values would have been present. However, the measured values at a median time of 70 seconds after birth were similar to values reported in 2week old infants.27 Several studies have described the various breathing patterns newborn infants use at birth to achieve lung aeration. We compared the 6 described breathing patterns by te Pas et al with ECO2 values and found no significant difference between the groups.3 Palme-Kilander et al found no significant difference in CO2 production and oxygen consumption with different breathing patterns.25 A synchrotron study showed similar results, the majority of lung aeration occurs during inspiration over multiple breaths.8 Our data suggest that although newborn infants use various breathing patterns to achieve lung aeration, it does not affect ECO2 values. Using a mainstream CO2 analyzer attached to a facemask to measure ECO2 has some limitations. Although, the rapid response time is an advantage, additional dead space can increase work of breathing.28 Recent studies measuring spontaneous breathing patterns in newborn infants used 2 L/min of bias flow to adjust for the increased dead space.3 In the current study, we did not use bias flow as this would have diluted CO2 in the expired gas and potentially caused underestimation of ECO2 values. In addition, mask leak might lead to lower measures of ECO2, which is a limitation of any CO2detector. During each recording, we closely monitored all infants breathing efforts for any signs of respiratory distress or apnea (Figure 6; available at www.jpeds.com). Clinically, heart rate is used to assess the effectiveness of ventilation in both spontaneously breathing and ventilated infants. Adding heart rate measurements would have strengthened the current study. The small number of 20 included infants is a further limitation of our study. However, measuring physiological changes in the delivery room is difficult, particularly because separation from the mother may 848
Vol. 166, No. 4 potentially interfere with bonding. To minimize mother and infant separation, we positioned the infants on the mother’s chest. This was well tolerated by all infants and parents. In addition, they were more likely to agree to participate in this research study, and it did not interfere with our measurements. We excluded infants delivered via cesarean because of the delay between clamping the cord and start of our measurement. n Submitted for publication Jul 9, 2014; last revision received Oct 13, 2014; accepted Dec 3, 2014.
References 1. Hooper SB, Kitchen MJ, Siew M, Lewis RA, Fouras A, te Pas A, et al. Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging. Clin Exp Pharmacol Physiol 2009;36: 117-25. 2. te Pas A, Davis PG, Hooper SB, Morley CJ. From liquid to air: breathing after birth. J Pediatr 2008;152:607-11. 3. Dawson JA, te Pas A, Wong C, Kamlin O, Morley CJ, Davis PG. Breathing patterns in preterm and term infants immediately after birth. Pediatr Res 2009;65:352-6. 4. Kattwinkel J, Perlman J, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S909-19. 5. Poulton DA, Schm€ olzer GM, Morley CJ, Davis PG. Assessment of chest rise during mask ventilation of preterm infants in the delivery room. Resuscitation 2011;82:175-9. 6. Schm€ olzer GM, Kamlin O, O’Donnell CP, Dawson JA, Morley CJ, Davis PG. Assessment of tidal volume and gas leak during mask ventilation of preterm infants in the delivery room. Arch Dis Child Fetal Neonatal 2010;95:F393-7. 7. Schm€ olzer GM, Morley CJ, Wong C, Dawson JA, Kamlin O, Donath S, et al. Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study. J Pediatr 2012; 160:377-81.e2. 8. Hooper SB, Fouras A, Siew M, Wallace MJ, Kitchen MJ, Pas te A, et al. Expired CO2 levels indicate degree of lung aeration at birth. PLoS One 2013;8:e70895. 9. van Os S, Cheung PY, Pichler G, Aziz K, O’Reilly M, Schm€ olzer GM. Exhaled carbon dioxide can be used to guide respiratory support in the delivery room. Acta Paediatr 2014;103:796-806. 10. Kang LJ, Cheung PY, Pichler G, OReilly M, Aziz K, Schm€ olzer GM. Monitoring lung aeration during respiratory support in preterm infants at birth. PLoS One 2014;9:e102729. 11. Garey DM, Ward R, Rich W, Heldt G, Leone TA, Finer N. Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates. Pediatrics 2008;121:e1524-7. 12. Schm€ olzer GM, Dawson JA, Poulton DA, Kamlin O, Morley CJ, Davis PG. Assessment of flow waves and colorimetric CO2 detector for endotracheal tube placement during neonatal resuscitation. Resuscitation 2011;82:307-12. 13. Leone TA, Lange A, Rich W, Finer N. Disposable colorimetric carbon dioxide detector use as an indicator of a patent airway during noninvasive mask ventilation. Pediatrics 2006;118:e202-4. 14. Finer N, Rich W, Wang C, Leone TA. Airway obstruction during mask ventilation of very low birth weight infants during neonatal resuscitation. Pediatrics 2009;123:865-9. 15. Kong JY, Rich W, Finer N, Leone TA. Quantitative end-tidal carbon dioxide monitoring in the delivery room: a randomized controlled trial. J Pediatr 2013;163:104-8.e1. 16. Hawkes GA, Kelleher J, Ryan CA, Dempsey EM. A review of carbon dioxide monitoring in preterm newborns in the delivery room. Resuscitation 2014;85:1-5.
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April 2015 17. Elm Von E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61: 344-9. 18. O’Donnell CP, Kamlin O, Davis PG, Morley CJ. Crying and breathing by extremely preterm infants immediately after birth. J Pediatr 2010;156: 846-7. 19. Boon AW, Milner AD, Hopkin IE. Lung expansion, tidal exchange, and formation of the functional residual capacity during resuscitation of asphyxiated neonates. J Pediatr 1979;95:1031-6. 20. Vyas H, Field D, Milner AD, Hopkin IE. Determinants of the first inspiratory volume and functional residual capacity at birth. Pediatr Pulmonol 1986;2:189-93. 21. Karlberg P, Koch G, Cherry RB, Escardo FE. Respiratory studies in newborn infants. II: pulmonary ventilation and mechanics of breathing in the first minutes of life, including the onset of respiration. Acta Paediatr 1962;51:121-36.
22. Engstr€ om L, Karlberg P, Rooth G. Influence of onset of respiration on blood gases and acid base balance in the newborn infant. Acta Obstet Gynecol Scand 1963;42(S6):46. 23. Karlberg P, Koch G, Wallgren G, Geubelle F. Respiratory studies in newborns. Acta Paediatr Suppl 1959;48(Suppl 118):128-30. 24. Palme-Kilander C, Tunell R. Pulmonary gas exchange during facemask ventilation immediately after birth. Arch Dis Child 1993;68:11-6. 25. Palme-Kilander C, Tunell R, Chiwei Y. Pulmonary gas exchange immediately after birth in spontaneously breathing infants. Arch Dis Child 1993;68:6-10. 26. Murthy V, O’Rourke-Potocki A, Dattani N, Fox GF, Campbell ME, Milner AD, et al. End tidal carbon dioxide levels during the resuscitation of prematurely born infants. Early Hum Dev 2012;88:783-7. 27. Wu CH, Chou HC, Hsieh WS, Chen WK, Huang PY, Tsao PN. Good estimation of arterial carbon dioxide by end-tidal carbon dioxide monitoring in the neonatal intensive care unit. Pediatr Pulmonol 2003;35:292-5. 28. Anderson CT, Breen PH. Carbon dioxide kinetics and capnography during critical care. Crit Care 2000;4:207-15.
50 Years Ago in THE JOURNAL OF PEDIATRICS Calorie Intake of Children with Down’s Syndrome (Mongolism) (sic) Culley WJ, Goyal K, Jolly DH, Mertz ET. J Pediatr 1965;66:772-5
F
ifty years ago, Culley et al tried to answer a complicated question about optimal calorie intake for small children with Down syndrome at a state-operated home in rural Indiana. They meticulously measured calorie intake over a 2-week period. Although a residential facility would provide an opportunity to monitor caloric intake and growth in a controlled setting, the investigators encountered a challenge that persists in today’s complicated world: How can we possibly understand optimal growth in our patients who suffer from countless conditions, genetic and otherwise, that affect growth? Challenges started with identifying weight status in patients during an era where body mass index was not a uniformly accepted measure. Employing bomb calorimetry, calculating calorie content of proteins based on nitrogen content, and depending on a limited US Department of Agriculture handbook, the team made estimates of calorie intake for the 23 subjects. Total intake was strictly controlled leading to questions about the representativeness of these feeding techniques for daily practice. The study by Culley et al led to a conclusion that calorie intake for patients with genetic syndromes should be made based on the patient’s height and not weight or body surface area. This work furthered an understanding that children with special healthcare needs should be viewed through the prism of their disease. If genetics makes them smaller, then that should be taken into account when addressing nutrition. This study is a reminder that the discipline of nutrition research has come very far. Although body mass index may not be a perfect measure of weight status for many reasons (degree of adiposity, inaccuracy at extremes of height and weight, etc), it is the imperfect language we all speak, and therefore understand, warts and all. There may be discussion about how best to use mandated nutrition information, but the challenge now is how best to manage information, not simply find it. Techniques for dietary recall have become more accurate through the use of technology and advances in behavior research. In addition, our high degree of interconnectedness allows us to glean more accurate information because we can access larger and more diverse populations to determine what “normal” really is. The fields of nutrition and weight research have many questions to answer. Thankfully, we live in an age where improved quantity and quality of data will permit us to answer these challenging questions. Christopher F. Bolling, MD Pediatric Associates, PSC Crestview Hills, Kentucky Division of General and Community Pediatrics Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio http://dx.doi.org/10.1016/j.jpeds.2014.10.013
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Figure 3. A prolonged expiration against a partially closed glottis (almost a prolonged grunt), which is indicated by the increasing CO2 and the slow expiratory flow. VTe, tidal volume.
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Figure 4. Gas flow, VTe, and ECO2 waveforms. No changes in ECO2 waveform are observed during crying.
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Figure 6. Apneic episode of 8 seconds. An increase in ECO2 can be observed after the apneic episode compared with the prior episode.
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B
efore birth, the airways are liquid-filled, and the lungs take no part in gas exchange, which occurs across the placenta.1,2 At birth, lung liquid has to be cleared from the airways to allow air entry and establishment of a functional residual capacity (FRC).1,2 Although much airway liquid can be removed before birth, a significant amount remains in the airways and its removal after birth is dependent on the infant’s respiratory effort.2 In the minutes after birth, the liquid within the airways is gradually cleared and replaced by air. Term and preterm infants use several different breathing patterns immediately after birth to achieve lung aeration.3 However, when infants fail to breathe adequately immediately after birth, it is important to apply positive pressure ventilation sufficient to facilitate gas exchange but without causing lung injury.4 At present, very little information is available to the clinician to assess the effectiveness of positive pressure ventilation.5,6 Clinicians lack feedback from either the patient or standard monitoring equipment to achieve the desired balance of aerating the distal gas exchange units (alveoli) without over-distending the lung thereby causing lung injury.7,8 Carbon dioxide (CO2) is produced in the tissues, transported to the lung, and exhaled from the lung. Therefore, CO2 can only be detected in expired gas if the lung is aerated, effective gas exchange has occurred, and adequate cardiac output is present.8-10 Hooper et al recently described how exhaled CO2 (ECO2) levels are an important indicator of ventilation of the distal gas exchange units.8 Several studies reported the use of ECO2 monitoring during neonatal transition to: (1) determine correct tube placement11,12; (2) identify airway obstruction13,14; (3) using CO2 targeting during mask ventilation15; or (4) assessing lung aeration in preterm infants.8-10,16 No study has reported ECO2 values in the first minutes after birth in term infants. The aim of the study was to measure the amount of ECO2 in term infants in the first 120 seconds after birth.
Methods All infants were born at The Royal Women’s Hospital, Melbourne, Australia, a tertiary perinatal center where 7300 infants are born each year. Infants who were >37 weeks postmenstrual age were eligible for the study. Consent was requested before birth and if the mother was not in established labor. Infants were excluded from final analysis if they had a congenital abnormality that might adversely affect their breathing. The Royal Women’s Hospital Research and Ethics Committees approved the study. The NICO Cardiopulmonary management system (Novametrix Medical System, Wallingford, Connecticut) consists of a combined CO2/flow sensor, which CO2 ECO2 FRC
Carbon dioxide Exhaled CO2 Functional residual capacity
From the 1Center for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Canada; 2Neonatal Services, The Royal Women’s Hospital; 3The Ritchie Center, Monash University, Melbourne, Australia; 4Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 5Critical Care Stream, Murdoch Children Research Institute; and 6Department of Obstetrics and Gynecology, The University of Melbourne, Melbourne, Australia Supported by the Laerdal Foundation for Acute Medicine (Stavanger, Norway). G.S. is supported in part by a Banting Postdoctoral Fellowship, Canadian Institute of Health Research. P.D. and S.H. are supported by an Australian National Health and Medical Research Council Practitioner and Principal Research Fellowship, respectively, and the Australian National Health and Medical Research Council Program (No. 384100). C.K. is supported by an Australian National Health and Medical Research Early Career Fellowship. S.H. was supported by the Victorian Government’s Operational Infrastructure Support Program. The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.12.007
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Vol. 166, No. 4 April 2015 measured ECO2 by infrared absorbance and gas flow, tidal volume, respiratory rate, and airway pressures with a flow sensor. The dead space of the CO2/flow sensor is 1 mL. The CO2/flow sensor was attached to a facemask (Laerdal round mask; Laerdal, Stavanger, Norway). Immediately after birth, the infants were placed on the mother’s chest, and the facemask was placed on the infants face to cover the mouth and the nose. This procedure was performed before the cord was clamped. To minimize interference with parentinfant bonding and to allow standard assessments and monitoring of term infants at birth, we only took measurements for the first 120 seconds from birth. If there were any signs of respiratory compromise, the study was abandoned and respiratory support was given according to the Neonatal Resuscitation guidelines.4 Data Collection and Analyses All recordings in the delivery room were performed by G.S. Time of birth was defined as delivery of the whole baby. The signals of airway flow, tidal volume, airway pressure, and ECO2 were recorded at 200 Hz using Spectra physiological recording program (a customized neonatal respiratory physiology program). Demographic characteristics of study infants were recorded. A breath-by-breath analysis was performed manually for the duration of each recording. Tidal volume, inflation time, gas flow, and ECO2 were measured. Breaths were excluded if mask leak was >30%. The data are presented as mean ( SD) for normally distributed continuous variables and median (IQR) when the distribution was skewed. For all respiratory variables, the mean value for each infant was calculated first and then either the mean or median of the median calculated. The clinical characteristics and outcome variables were compared using
Student t-test for parametric and Mann-Whitney U-test for nonparametric comparisons for continuous variables, and c2 for categorical variables. ECO2 values during different breathing patterns were compared using repeated measures ANOVA with Bonferroni post-test. P values are 2-sided, and P < .05 was considered statistically significant. Statistical analyses were performed with Stata (Intercooled 10; StataCorp, College Station, Texas). The study was reported according to The Strengthening the Reporting of Observational Studies in Epidemiology statement guidelines.17
Results We included a convenience sample of 20 term infants. All infants initiated spontaneous breathing, and none required respiratory support, intubation, chest compressions, or epinephrine. The mean (SD) birth weight was 2976 (697) g, and gestational age 38 (2) weeks. Seven infants (35%) were male and the median (IQR) 1 and 5 minute Apgar scores were 9 (7; 9) and 9 (9; 10), respectively. A total of 1129 breaths were analyzed, with a median (IQR) of 54 (42-69) per infant. The face mask was placed over the baby’s mouth and nose at a median (IQR) of 5 (3-8) seconds after birth. CO2 ECO2 was first detected at a median (range) of 3 (1-8) breaths or 15 (12-22) seconds after birth (Table). Within the next 10 breaths, CO2 increased significantly to 27 (22-34) mm Hg in all infants (P < .0001) (Table and Figures 1 and 2). Three infants had significantly less measured ECO2 in the first 10 breaths compared with the other 17 infants (Table). Increases in ECO2 were associated with increases in tidal
Table. Tidal volume, exhaled CO2, and mask leak during the first 120 seconds ID number (n = 20) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Number of breaths without ECO2
VTe (mL/kg) without ECO2
VTe (mL/kg) from the first 10 breaths with ECO2
P values for comparison of VTe with and without CO2
3 3 8 4 1 1 8 2 1 0 2 5 1 5 1 1 2 1 0 2
0.9 (0.6-4.0) 0.9 (0.6-4.0) 2.5 (1.5-3.5) 0.8 (0.5-1.3) 3.7 0.8 2.1 (0.8-2.9) 0.5 0.3 0.7 (0.6-0.8) 0.9 (0.7-2.9) 0.6 1.6 (1.2-2.1) 3.1 6.3 0.6 0.3 0.8 (0.7-0.9)
11.4 (6.7-12.7) 12.1 (6.9-13.2) 13.4 (6.6-20.3) 7.7 (3.1-10.4) 10.7 (9.7-11.6) 1.1 (0.8-1.7) 6.3 (1.9-11.7) 9.6 (4.0-11.2) 2.5 (2.4-3.3) 4.6 (3.8-4.9) 7.0 (6.7-8.3) 12.5 (6.0-14.2) 3.7 (1.2-7.1) 1.4 (1.1-2.8) 10.8 (4.4-16.5) 1.9 (0.9-2.4) 11.0 (4.6-12.8) 2.4 (2.2-3.1) 4.6 (3.8-5.0) 7.8 (7.4-9.2)
.0078 .0084 .0015 .0289 .0165
.0076 .0032 .6163
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ECO2 (mm Hg)
Mask leak (%)
21 (18-24)* 22.5 (13-25)* 31 (28-35)* 25 (20-26)* 29 (26-33)* 12 (8-14)* 50 (20-53)* 53 (50-57)* 34 (27-43)* 22 (18-30)* 27 (17-38)* 36 (35-40)* 29 (20-42)* 8 (7-10)* 26 (10-35)* 8.5 (7-10)* 52 (49-57)* 33 (27-42)* 22 (18-29)* 26 (17-37)*
23 (16) 22 (15) 33 (23) 24 (24) 20 (14) 38 (25) 43 (25) 26 (20) 12 (9) 36 (21) 27 (20) 17 (13) 24 (17) 27 (17) 34 (29) 28 (22) 26 (21) 12 (9) 35 (21) 26 (19)
ID, identification; VTe, expiratory tidal volume. Values are presented as median (IQR) unless indicated *mean (range).
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Vol. 166, No. 4 maximum ECO2 was 51 (40-73) mm Hg at 70 (21-106) seconds after birth. ECO2 at 60 and 120 seconds after birth was 41 (7) and 43 (10) mm Hg, respectively (Figure 1). Overall no difference in ECO2 between different breathing patterns was found. The median (IQR) ECO2 during expiratory breath hold was 38 (31-43) mm Hg vs 40 (30-47) mm Hg during slow expiration (Figure 3; available at www.jpeds. com), 33 (10-40) mm Hg during crying (Figure 4; available at www.jpeds.com), 35 (30-40) mm Hg during grunting, 35 (28-40) mm Hg during normal breaths (Figure 5), and 32 (26-40) mm Hg during panting, respectively.
Figure 1. Course of mean (SD) ECO2 (mm Hg) and VTe (mL/kg). Breaths after birth (0-1 = No CO2; 1-10 = the first 10 breaths with CO2; and at 60 and 120 seconds of recording). VTe, tidal volume.
volume in most (17/20) infants. Two infants did not show an increase in tidal volume before and after ECO2 was detected. Only 1 infant showed a decrease in expired tidal volume when ECO2 was first detected. The median (range) of
Tidal Volume Infants initiated spontaneous breathing at a median (range) of 9 (2-33) seconds after birth. The median (IQR) tidal volume during breaths without CO2 was 1.2 (0.8-3.1) mL/kg compared with 7.3 (3.2-10.9) mL/kg during the first 10 breaths where CO2 was exhaled (Table). The tidal volume at 60 and 120 seconds after birth was 5.4 (4) and 6.3 (3) mL/kg, respectively (Figure 1). Inspiration Time The median (IQR) inspiration time during breaths with no CO2 was similar compared with breaths with ECO2 0.19 (0.14-0.6) second vs 0.29 (0.24-0.34) second, respectively (P = .16). Gas Flow The inspired and expired gas flow significantly increased in the first 10 breaths with ECO2 compared with breaths with
Figure 2. Spontaneously breathing 38 weeks term infant with VTe breaths of 6.1-7.7 mL/kg. The ECO2 is around 5-10 mm Hg. Once the cord is clamped, spontaneous VTe are similar. However, a rapid increase in CO2 to 50-70 mm Hg is observed. 846
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Figure 5. Inspiration is identified by a steep incline in the gas flow wave and the VTe wave. The CO2 wave remains at baseline until the start of expiration, which can be identified with a sharp increase in the CO2 wave, a negative gas flow wave, and decline in VTe wave.
no CO2. Median (IQR) inspired flow when CO2 was not detected in the subsequent expired gas, was 30 (21-36) mL/s compared with 107 (49-147) mL/s when CO2 was detected (P = .003). Expiratory flow significantly increased from 42 ( 51 to 33) mL/s in breaths without CO2 compared with 92 ( 99 to 67) mL/s in breaths with CO2 (P = .023).
Discussion In utero, the airways are liquid-filled and the lungs do not take part in gas exchange, which occurs across the placenta. At birth, lung liquid has to be cleared from the airways to allow air entry to generate FRC and facilitate gas exchange. The majority of newborn infants cry at birth,18 leading to establishment of FRC and initiation of spontaneous breathing. Boon et al reported that only 5/20 asphyxiated newborn infants generated FRC with the first inflation,19 which is contrary to Vyas et al who reported that all 9 asphyxiated newborn infants established FRC with the first inflation.20 Studies of spontaneously breathing infants immediately after birth reported that the first breaths tend to be deeper and longer than subsequent breaths and are characterized by a short deep inspiration followed by a prolonged expiratory
phase. Vyas et al demonstrated that 15/16 infants were able to establish FRC with the first breath.20 However, it remains unclear whether those first breaths facilitate gas exchange. We have measured ECO2 immediately after birth (Figure 1) and before the umbilical cord was clamped (Figure 2) in 20 term infants to determine when lung aeration and gas exchange occurs. Compared with previously published studies, in our study, tidal volumes for the first breaths (Table) were small, ranging from 0.4-6.3 mL/kg. However, all infants took these first breaths while still attached to the umbilical cord (Figure 2). This may have indirectly contributed to the lower tidal volumes as a result of sustained placental gas exchange reducing the respiratory drive associated with increased circulating CO2 levels. Once the cord was clamped and tidal volume significantly increased, we were able to detect and measure ECO2 (Table). The volume of all consecutive breaths were similar to previously published studies.3,20-23 In addition, we observed a significant increase in expiratory and inspiratory gas flow in the first breaths with ECO2 compared with breaths without ECO2. Similar observation has been reported in phase contrast imaging studies.1,8 With each inspiratory effort, the air/liquid interface progressed deeper into the distal airways, thereby
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drawing air deeper into the respiratory tree.1 This could explain the significant increase in gas flow between unaerated and aerated breaths. In addition, end-expiratory lung volume increases with each breath, which could be an explanation for the observed larger tidal volumes in the breaths with ECO2. In the current study, all infants cried soon after birth, and we were able to record the first breath in all included infants. Overall, it took a median of 3 breaths until the first ECO2 was detected (Table). Once ECO2 was detected, levels increased significantly within the first 10 breaths (Figure 1). Similar results have been reported in studies measuring CO2 elimination in term and preterm infants.9,10,24-26 Our increase in ECO2 was related to increase in tidal volume, and inspiratory and expiratory gas flow. Overall, it took a median time of 70 seconds from birth until maximum ECO2 values were measured. These results are similar to previously reported values of CO2 elimination in term infants, which reached a maximum around 90-120 seconds after birth.25 However, preterm infants require a long period to achieve similar CO2 elimination values.10,24 We only recorded the first 120 seconds after birth, hence, we do not know if potentially higher ECO2 values would have been present. However, the measured values at a median time of 70 seconds after birth were similar to values reported in 2week old infants.27 Several studies have described the various breathing patterns newborn infants use at birth to achieve lung aeration. We compared the 6 described breathing patterns by te Pas et al with ECO2 values and found no significant difference between the groups.3 Palme-Kilander et al found no significant difference in CO2 production and oxygen consumption with different breathing patterns.25 A synchrotron study showed similar results, the majority of lung aeration occurs during inspiration over multiple breaths.8 Our data suggest that although newborn infants use various breathing patterns to achieve lung aeration, it does not affect ECO2 values. Using a mainstream CO2 analyzer attached to a facemask to measure ECO2 has some limitations. Although, the rapid response time is an advantage, additional dead space can increase work of breathing.28 Recent studies measuring spontaneous breathing patterns in newborn infants used 2 L/min of bias flow to adjust for the increased dead space.3 In the current study, we did not use bias flow as this would have diluted CO2 in the expired gas and potentially caused underestimation of ECO2 values. In addition, mask leak might lead to lower measures of ECO2, which is a limitation of any CO2detector. During each recording, we closely monitored all infants breathing efforts for any signs of respiratory distress or apnea (Figure 6; available at www.jpeds.com). Clinically, heart rate is used to assess the effectiveness of ventilation in both spontaneously breathing and ventilated infants. Adding heart rate measurements would have strengthened the current study. The small number of 20 included infants is a further limitation of our study. However, measuring physiological changes in the delivery room is difficult, particularly because separation from the mother may 848
Vol. 166, No. 4 potentially interfere with bonding. To minimize mother and infant separation, we positioned the infants on the mother’s chest. This was well tolerated by all infants and parents. In addition, they were more likely to agree to participate in this research study, and it did not interfere with our measurements. We excluded infants delivered via cesarean because of the delay between clamping the cord and start of our measurement. n Submitted for publication Jul 9, 2014; last revision received Oct 13, 2014; accepted Dec 3, 2014.
References 1. Hooper SB, Kitchen MJ, Siew M, Lewis RA, Fouras A, te Pas A, et al. Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging. Clin Exp Pharmacol Physiol 2009;36: 117-25. 2. te Pas A, Davis PG, Hooper SB, Morley CJ. From liquid to air: breathing after birth. J Pediatr 2008;152:607-11. 3. Dawson JA, te Pas A, Wong C, Kamlin O, Morley CJ, Davis PG. Breathing patterns in preterm and term infants immediately after birth. Pediatr Res 2009;65:352-6. 4. Kattwinkel J, Perlman J, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S909-19. 5. Poulton DA, Schm€ olzer GM, Morley CJ, Davis PG. Assessment of chest rise during mask ventilation of preterm infants in the delivery room. Resuscitation 2011;82:175-9. 6. Schm€ olzer GM, Kamlin O, O’Donnell CP, Dawson JA, Morley CJ, Davis PG. Assessment of tidal volume and gas leak during mask ventilation of preterm infants in the delivery room. Arch Dis Child Fetal Neonatal 2010;95:F393-7. 7. Schm€ olzer GM, Morley CJ, Wong C, Dawson JA, Kamlin O, Donath S, et al. Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study. J Pediatr 2012; 160:377-81.e2. 8. Hooper SB, Fouras A, Siew M, Wallace MJ, Kitchen MJ, Pas te A, et al. Expired CO2 levels indicate degree of lung aeration at birth. PLoS One 2013;8:e70895. 9. van Os S, Cheung PY, Pichler G, Aziz K, O’Reilly M, Schm€ olzer GM. Exhaled carbon dioxide can be used to guide respiratory support in the delivery room. Acta Paediatr 2014;103:796-806. 10. Kang LJ, Cheung PY, Pichler G, OReilly M, Aziz K, Schm€ olzer GM. Monitoring lung aeration during respiratory support in preterm infants at birth. PLoS One 2014;9:e102729. 11. Garey DM, Ward R, Rich W, Heldt G, Leone TA, Finer N. Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates. Pediatrics 2008;121:e1524-7. 12. Schm€ olzer GM, Dawson JA, Poulton DA, Kamlin O, Morley CJ, Davis PG. Assessment of flow waves and colorimetric CO2 detector for endotracheal tube placement during neonatal resuscitation. Resuscitation 2011;82:307-12. 13. Leone TA, Lange A, Rich W, Finer N. Disposable colorimetric carbon dioxide detector use as an indicator of a patent airway during noninvasive mask ventilation. Pediatrics 2006;118:e202-4. 14. Finer N, Rich W, Wang C, Leone TA. Airway obstruction during mask ventilation of very low birth weight infants during neonatal resuscitation. Pediatrics 2009;123:865-9. 15. Kong JY, Rich W, Finer N, Leone TA. Quantitative end-tidal carbon dioxide monitoring in the delivery room: a randomized controlled trial. J Pediatr 2013;163:104-8.e1. 16. Hawkes GA, Kelleher J, Ryan CA, Dempsey EM. A review of carbon dioxide monitoring in preterm newborns in the delivery room. Resuscitation 2014;85:1-5.
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April 2015 17. Elm Von E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61: 344-9. 18. O’Donnell CP, Kamlin O, Davis PG, Morley CJ. Crying and breathing by extremely preterm infants immediately after birth. J Pediatr 2010;156: 846-7. 19. Boon AW, Milner AD, Hopkin IE. Lung expansion, tidal exchange, and formation of the functional residual capacity during resuscitation of asphyxiated neonates. J Pediatr 1979;95:1031-6. 20. Vyas H, Field D, Milner AD, Hopkin IE. Determinants of the first inspiratory volume and functional residual capacity at birth. Pediatr Pulmonol 1986;2:189-93. 21. Karlberg P, Koch G, Cherry RB, Escardo FE. Respiratory studies in newborn infants. II: pulmonary ventilation and mechanics of breathing in the first minutes of life, including the onset of respiration. Acta Paediatr 1962;51:121-36.
22. Engstr€ om L, Karlberg P, Rooth G. Influence of onset of respiration on blood gases and acid base balance in the newborn infant. Acta Obstet Gynecol Scand 1963;42(S6):46. 23. Karlberg P, Koch G, Wallgren G, Geubelle F. Respiratory studies in newborns. Acta Paediatr Suppl 1959;48(Suppl 118):128-30. 24. Palme-Kilander C, Tunell R. Pulmonary gas exchange during facemask ventilation immediately after birth. Arch Dis Child 1993;68:11-6. 25. Palme-Kilander C, Tunell R, Chiwei Y. Pulmonary gas exchange immediately after birth in spontaneously breathing infants. Arch Dis Child 1993;68:6-10. 26. Murthy V, O’Rourke-Potocki A, Dattani N, Fox GF, Campbell ME, Milner AD, et al. End tidal carbon dioxide levels during the resuscitation of prematurely born infants. Early Hum Dev 2012;88:783-7. 27. Wu CH, Chou HC, Hsieh WS, Chen WK, Huang PY, Tsao PN. Good estimation of arterial carbon dioxide by end-tidal carbon dioxide monitoring in the neonatal intensive care unit. Pediatr Pulmonol 2003;35:292-5. 28. Anderson CT, Breen PH. Carbon dioxide kinetics and capnography during critical care. Crit Care 2000;4:207-15.
50 Years Ago in THE JOURNAL OF PEDIATRICS Calorie Intake of Children with Down’s Syndrome (Mongolism) (sic) Culley WJ, Goyal K, Jolly DH, Mertz ET. J Pediatr 1965;66:772-5
F
ifty years ago, Culley et al tried to answer a complicated question about optimal calorie intake for small children with Down syndrome at a state-operated home in rural Indiana. They meticulously measured calorie intake over a 2-week period. Although a residential facility would provide an opportunity to monitor caloric intake and growth in a controlled setting, the investigators encountered a challenge that persists in today’s complicated world: How can we possibly understand optimal growth in our patients who suffer from countless conditions, genetic and otherwise, that affect growth? Challenges started with identifying weight status in patients during an era where body mass index was not a uniformly accepted measure. Employing bomb calorimetry, calculating calorie content of proteins based on nitrogen content, and depending on a limited US Department of Agriculture handbook, the team made estimates of calorie intake for the 23 subjects. Total intake was strictly controlled leading to questions about the representativeness of these feeding techniques for daily practice. The study by Culley et al led to a conclusion that calorie intake for patients with genetic syndromes should be made based on the patient’s height and not weight or body surface area. This work furthered an understanding that children with special healthcare needs should be viewed through the prism of their disease. If genetics makes them smaller, then that should be taken into account when addressing nutrition. This study is a reminder that the discipline of nutrition research has come very far. Although body mass index may not be a perfect measure of weight status for many reasons (degree of adiposity, inaccuracy at extremes of height and weight, etc), it is the imperfect language we all speak, and therefore understand, warts and all. There may be discussion about how best to use mandated nutrition information, but the challenge now is how best to manage information, not simply find it. Techniques for dietary recall have become more accurate through the use of technology and advances in behavior research. In addition, our high degree of interconnectedness allows us to glean more accurate information because we can access larger and more diverse populations to determine what “normal” really is. The fields of nutrition and weight research have many questions to answer. Thankfully, we live in an age where improved quantity and quality of data will permit us to answer these challenging questions. Christopher F. Bolling, MD Pediatric Associates, PSC Crestview Hills, Kentucky Division of General and Community Pediatrics Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio http://dx.doi.org/10.1016/j.jpeds.2014.10.013
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Figure 3. A prolonged expiration against a partially closed glottis (almost a prolonged grunt), which is indicated by the increasing CO2 and the slow expiratory flow. VTe, tidal volume.
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Figure 4. Gas flow, VTe, and ECO2 waveforms. No changes in ECO2 waveform are observed during crying.
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Figure 6. Apneic episode of 8 seconds. An increase in ECO2 can be observed after the apneic episode compared with the prior episode.
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